103 Stickler Syndrome
Stickler dysplasia, hereditary progressive Differential Diagnosis arthro-ophthalmopathy, • Marshall syndrome Stickler arthro-ophthalmopathy • Otospondylomegaepiphyseal dysplasia (OSMED) • Spondyloepiphyseal dysplasia congenita Flat midface, congenital myopia, cleft palate, hearing • Neonatal form of Kniest dysplasia loss, enlarged joints Radiographic Features: Frequency: 1 in 20,000 births. 1. Infancy Limbs Genetics • Widened metaphyses, especially of femurs and Autosomal dominant (OMIM 108300); Stickler type tibias I, with eye changes, is due to mutations of the Spine COL2A1 gene, which maps to 12q13.11-q13.2; Stick- • Coronal cleft vertebrae ler type II (beaded-vitreous type, OMIM 604841) is caused by mutations of the COL11A1 gene mapped to Radiographic Features: chromosome 1p21 (allelic to Marshall syndrome); 2. Childhood Stickler type III (nonocular type, OMIM 184840) is Spine caused by mutations in the COL11A2 gene at chro- • Mild platyspondyly, occasionally with end-plate mosome 6p21.3, and is the same entity as Weissen- irregularities resembling those of Scheuermann bacher-Zweymüller syndrome (allelic to OSMED). disease • Anterior wedging of vertebral bodies Clinical Features • Kyphosis (thoracic), mild to moderate scoliosis Highly variable, often manifesting in infancy or early Limbs childhood • Undermodeled long tubular bones, with broad • May present in neonates as Pierre-Robin sequence metaphyses and epiphyses, especially of femurs • Marfanoid or short, stocky habitus and proximal tibias • Normal rounded head, flat facies, facial asymme- • Relatively thin cortices try • Dysharmonic ossification of the carpal bones • Epicanthal folds, congenital often nonprogressive Pelvis high-degree myopia, vitreoretinal changes, retinal • Coxa valga detachment, glaucoma • Wide femoral necks • Flat nasal bridge • Protrusio acetabuli • Cleft palate (25%), glossoptosis • Hypoplasia of iliac wings • Micrognathia • Sensorineural hearing loss, recurrent otitis Radiographic Features: • Mitral valve prolapse 3. Adulthood • Hyperextensible joints, prominent painful joints, • Secondary degenerative arthropathy,most notably morning stiffness, progressive osteoarthritis of weight-bearing joints • Relative arachnodactyly, genu valgum Stickler Syndrome 903
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Fig. 103.1. a Patient 1, a child. Note flat midface, depressed nasal bridge, and micrognathia (Re- printed, with permission, from Spranger 1998); b, c Patient 2, an adolescent. Normal head, flat midface, severe myopia, slight micrognathia, and c prominent ears
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Fig. 103.2. Patient 3, age 5 years. Slightly flattened, otherwise nor- mal lumbar vertebrae. (Reprinted, with permission, from Spranger 1998.) b Patient 4, age 34 years. Note vertebral flattening with mild thoracic kyphosis, and mar- ginal vertebral osteophytes (From Sebes and Kasthuri 2000)
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Bibliography Snead MP,Yates JR. Clinical and molecular genetics of Stickler syndrome. J Med Genet 1999; 36: 353–9 Canepa G, Maroteaux P,Pietrogrande V.Sindromi dismorfiche Spallone A. Stickler’s syndrome: a study of 12 families. Br J e malattie costituzionali dello scheletro. Piccin, Padova, Ophthalmol 1987; 71: 504–9 1996 Spranger J. Hereditary arthro-ophthalmopathy. Ann Radiol Hall J. Stickler syndrome presenting as a syndrome of cleft 1968; 11: 359–64 palate, myopia and blindness inherited as a dominant trait. Spranger J. The type XI collagenopathies. Pediatr Radiol 1998; Birth Defects Orig Art Ser 1974; 10: 157–71 28: 745–50 Herrmann J, France TD, Spranger JW,Opitz JM, Wiffler C. The Temple IK. Stickler’s syndrome. J Med Genet 1989; 26: 119–26 Stickler syndrome (hereditary arthro-ophthalmopathy). Vintiner GM, Temple IK, Middleton-Price HR, Baraitser M, Birth Defects Orig Art Ser 1975; 11: 76–103 Malcolm S. Genetic and clinical heterogeneity of Stickler Liberfarb RM, Hirose T, Holmes LB. The Wagner-Stickler syn- syndrome. Am J Med Genet 1991; 41: 44–8 drome: a study of 22 families. J Pediatr 1981; 99: 394–9 Zlotogora J, Sagi M, Schuper A, Leiba H, Merin S.Variability of Sebes JI, Kasthuri S. Hereditary arthro-ophthalmopathy Stickler syndrome. Am J Med Genet 1992; 42: 337–9 (Stickler syndrome). Skeletal Radiol 2000; 29: 613–6. Stickler Syndrome 905
Fig. 103.3. a Patient 3, at age 2 years. Note broad proximal femoral metaphyses and flat epi- physes, with coxa valga. (Re- printed, with permission, from Spranger 1998.) b Patient 5, age 10 years. Note flattening and scle- rosis of capital femoral epiphyses and bilateral coxa valga. (Reprint- ed, with permission, from Canepa et al. 1996)
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Fig. 103.4. a Patient 3,at age 6 years.Note mild shortening of the metacarpals and phalanges, and broad and flat meta- carpal epiphyses. (Reprinted, with permission, from Spranger 1998.) b Right hand and c left wrist, patient 4, age 34 years. Note flattening of the 3rd and 4th metacarpal heads (black arrows), shortening of the 5th metacarpal, bilateral ossifica- tion centers between the capitate and third metacarpals (open arrows),and soft tissue calcification at the ulnar side of c the hamate (arrowhead). (Reprinted, with permission, from Sebes and Kasthuri 2000)